Keywords
Abstract
Oxidative stress is closely related to the development of cancer, diabetes, neurodegeneration, cardio- vascular diseases and requires the administration of exogenous antioxidants (AOs). Derivatives of 2-oxoin- doline-3-glyoxylic acid can claim the role of synthetic AOs for complex therapy of diseases of the central nervous system and internal organs.
The aim of the study is to research AO effect of 2-hydroxy-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro- indol-3-ylidene)-acetamide (compound 18) under modeling of the heart and kidney pathology in labora- tory animals.
Two series of experiments were conducted on albino male rats. In the first series, adrenaline myocardi- tis was modeled. Compound 18 (12 mg/kg) and the reference preparation ethylmethylhydroxypyridine succinate (100 mg/kg) were administered intraperitoneally 30 min before and 1 h after the adrenaline administration. In the blood plasma, we studied the activity of enzymes-markers of cardiac pathology: creatine kinase (CK-MV), alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the plasma and myocardium, the parameters of lipid peroxidation (LPO) and AO protection. In the second series of experiments, glycerol-induced acute kidney injury was modeled 30–40 min after administration of the pharmacological agent. After 24 h, the content of creatinine and urea in blood plasma was studied, the intensity of LPO and the state of AO enzymes in the plasma and kidneys were evaluated. Statistical pro- cessing was carried out by Statistica 6.0 software, using ANOVA variance analysis.
Adrenaline myocarditis was characterized by an increase in the activity of CK-MV, AST and ALT against the intact control. This was accompanied by an increase in the content of LPO products that react with 2-thiobarbituric acid (TBA-AP) and inhibition of the activity of superoxide dismutase (SOD) and catalase. Compound 18 normalized the biochemical changes induced by adrenaline. There was a decrease in the activity of CK-MV, AST and ALT in comparison with the control pathology. Under the influence of compound 18, a decrease in the content of TBA-AP by 19 % and an increase in the activity of SOD by 17 % and cata- lase by 34 % were observed in the myocardium. It was superior to the reference preparation in terms of its effect on marker enzymes, lowering the level of TBA-AP and activation of catalase in the myocardium.
Modeling of glycerol-induced acute kidney injury was characterized by an increase in the content of creatinine and urea in the blood plasma, an increase in the content of TBA-AP in the blood plasma and kidneys with a decrease in the activity of catalase and SOD against the intact control. Compound 18 and the reference preparation did not cause a decrease in the content of creatinine and urea and the intensity of LPO in acute kidney injury. The content of TBA-AP in the blood plasma and kidneys did not differ from that in the control pathology, however, both drugs increased the activity of catalase in the kidneys.
Therefore, 2-hydroxy-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide (compound 18) under conditions of adrenaline myocarditis restores the level of biochemical markers of the myocardium state and inhibits the development of oxidative stress more effectively than ethylmethylhydroxypyridine suc- cinate. It is less active as a nephroprotector compared to its cardioprotective effect, however, even in the case of acute kidney damage, it increases the activity of the AO enzyme catalase.